You are on page 1of 19

PHYTOTHERAPY RESEARCH

Phytother. Res. 31: 819–837 (2017)


Published online 10 April 2017 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/ptr.5805

REVIEW
Effects of Avocado (Persea americana) on
Metabolic Syndrome: A Comprehensive
Systematic Review

Jamshid Tabeshpour,1,2 Bibi Marjan Razavi3 and Hossein Hosseinzadeh4*


1
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
2
Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
3
Targeted Drug Delivery Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University
of Medical Sciences, Mashhad, Iran
4
Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of
Medical Sciences, Mashhad, Iran

Metabolic syndrome (MetS) is a clustering of risk factors including high blood glucose, dyslipidemia,
hypertension, and obesity that lead to the increased risk of type 2 diabetes mellitus and cardiovascular diseases
(CVDs), which are among leading causes of death in the world. Metabolic syndrome increases the risk of type 2
diabetes mellitus and CVDs by approximately five and three folds, respectively. Therefore, it is of vital
importance to manage such conditions with herbal options which have less undesirable adverse effects and
may be more efficacious in comparison with synthetic options. Avocado is a well-known source of carotenoids,
minerals, phenolics, vitamins, and fatty acids. The lipid-lowering, antihypertensive, antidiabetic, anti-obesity,
antithrombotic, antiatherosclerotic, and cardioprotective effects of avocado have been demonstrated in several
studies. In this review, we aimed to find out avocado’s pharmacological effects on different components of MetS.
Moreover, this review report is performed on the MetS effects of peel, seed, flesh, and leaves of avocado.
Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: avocado; Persea americana; metabolic syndrome; cardiovascular diseases; obesity; diabetes.

Abbreviations: A1CE, angiotensin 1 converting enzyme; ADI, adiposity index; AID, alloxan-induced diabetic; ALP, alkaline
phosphatase; ALT, alanine transaminase; APTT, activated partial thromboplastin time; AST, aspartate transaminase; BGLs, blood
glucose levels; BMI, body mass index; BP, blood pressure; CAT, catalase; CVDs, cardiovascular diseases; DPPH, l, l-diphenyl,
2-picrylhydrazyl; FASN, fatty acid synthase; FBG, fasting blood glucose; GPx, glutathione peroxidase; GR, glutathione reductase;
HCD, high-cholesterol diet; HCh, hypercholesterolemic; HFD, high-fat diet; HR, heart rate; LPL, lipoprotein lipase; MDA,
malondialdehyde; MetS, Metabolic syndrome; P. Americana, Persea Americana; PLs, phospholipids; PPAR-γ, peroxisome
proliferator-activated receptor-γ; PT, prothrombin time; SID, streptozotocin-induced diabetic; SOD, superoxide dismutase; T2DM,
type 2 diabetes mellitus; TC, total cholesterol; TFP, total fat pad mass; TG, triglyceride, LDL-C, low-density lipoprotein cholesterol,
HDL-C, high-density lipoprotein cholesterol; VLDL, very-low-density lipoprotein

high-density lipoprotein cholesterol (HDL) < 1.0 mmol/


INTRODUCTION
L (male) or <1.3 mmol/L (female), triglyceride
(TG) > 1.7 mmol/L and waist circumference > 102 cm
Metabolic syndrome (MetS) is a clinical entity markedly (male) or >88 cm (female) (Malik et al., 2004; Grundy
heterogeneous, characterized by the co-occurrence et al., 2005).
of multiple changes in obesity, insulin-resistance, Medicinal plants have been used as an accepted
hypertension, and dyslipidemia, correlated with an complementary medical option for centuries to improve
enhanced risk of developing cardiovascular diseases the health condition of the folk through decreasing the
(CVDs) and type 2 diabetes mellitus (T2DM) (Wu et al., adverse effects and costs of the synthetic medicines
2010). Metabolic syndrome is regarded as an increasing (Hassani et al., 2016; Rouhi-Boroujeni et al., 2015). In
cause of morbidity and mortality in both developed and developing countries, more than 80% of the population
developing countries (Smith and Ryckman, 2015). There use traditional medicinal plants to treat a variety of
are several criteria set out by different associations for diseases (Rouhi-Boroujeni et al., 2015). Although
MetS definition and diagnosis. The most generally herbs are regarded as ‘natural’ and safe, many different
accepted definition consists of three or more of the side effects have been reported because of active
following indicators: blood pressure (BP) > 135/ ingredients, contaminants, or interactions with drugs.
85 mmHg, fasting blood glucose (FBG) > 6.1 mmol/L, Moreover, there is limited evidence regarding the use
of herbal medicines during pregnancy as well as in
* Correspondence to: Hossein Hosseinzadeh, Pharmaceutical Research
Center, Department of Pharmacodynamics and Toxicology, School of
pediatric and geriatric populations (Izzo et al., 2016).
Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. These days, plants are regarded as a valuable source to
E-mail: hosseinzadehh@mums.ac.ir treat the various components of MetS including obesity,
Received 16 January 2017
Revised 27 February 2017
Copyright © 2017 John Wiley & Sons, Ltd. Accepted 02 March 2017
820 J. TABESHPOUR ET AL.

hyperglycemia, hypertension, and dyslipidemia. In this phytostanols decreases the serum levels of cholesterol,
regard, it is very important to find and utilize medicinal because of similar structures, leading to the prevention
plants, and their constituents with beneficial effects on of CVDs and also potential protection in the number
MetS to replace with synthetic medicines. For instance, of cancer development (Awad and Fink, 2000;
cinnamon; garlic; grape; black cumin, saffron and its Piironen et al., 2000; Kritchevsky and Chen, 2005).
constituent, thymoquinone; and rutin have shown For instance, an in vitro study showed that the avocado
promising effects on MetS (Mollazadeh and pulp, specifically tocopherols, lutein, and other
Hosseinzadeh, 2016; Hosseini and Hosseinzadeh, 2015; carotenoids (as active constituents), possess growth
Akaberi and Hosseinzadeh, 2016; Razavi and inhibitory effects against cancer (Lu et al., 2009). Fig. 2
Hosseinzadeh, 2014; Hosseinzadeh and Nassiri-Asl, shows the structural comparison of the bioactive
2014; Razavi and Hosseinzadeh, 2016). Avocado with constituents of avocado such as phytosterols,
the scientific name of Persea americana (P. americana), phytostanols, and cholesterol. Some of the most
and other names such as ‘alligator pear’, ‘avocato’, abundant pharmacologically active constituents of
‘ahuacate’ etc., from the Lauraceae family, originated avocado phytochemicals are structurally shown in
in Mexico and Central or South America, is an Fig. 3. Our review aimed to evaluate the effect of
evergreen tree that can reach the height of 10 m or more different bioactive phytochemicals of avocado on
(Dreher and Davenport, 2013; Lacerda et al., 2015). It is various components of MetS including T2DM,
also known as ‘alligator pear’ or ‘butter pear’ (Lacerda hypertension, dyslipidemia, and obesity, and to
et al., 2015). Avocado is consumed, not only for its describe different mechanisms of action. Moreover, in
flavor, but also for its high nutritional value and this review, 186 articles were found, among which 129
beneficial health effects (Meyer and Terry, 2010) were revised and included (Fig. 1).
including hypoglycaemic (Ezejiofor et al., 2013a),
antihypertensive (Dzeufiet et al., 2014), antioxidant
(Nagaraj et al., 2010), anti-obesity (Monika and
Geetha, 2016), hypolipidemic (Pahua-Ramos et al., Effect on high glucose level
2012) (Fig. 4), antilithiasis (Wientarsih et al., 2012),
anticonvulsant (Ojewole and Amabeoku, 2006), Type 2 diabetes mellitus is known as a metabolic
antimicrobial (Pradeep et al., 2012), antiprotozoal and disorder which results from a failure in insulin secretion,
antimycobacterial (Jiménez-Arellanes et al., 2013), action or both (Rao and Adinew, 2011). This can lead
hepatoprotective (Mahmoed and Rezq, 2013), to micro-vascular and macro-vascular difficulties
antiosteoarthritis (Christiansen et al., 2015) and which chronically cause the malfunctioning of central
chemo-protective (Paul et al., 2011). and peripheral nervous system, kidney, eye, and
Avocado composition analysis has shown that this cardiovascular system (Brahmachari, 2011). Besides, it
plant is nutritionally valuable. The most important is one of the main causes of mortality, morbidity, and
bioactive phytochemicals of avocado are categorized health center costs in the world. According to the global
into: Carotenoids, fatty acids, minerals, phenolics reports on diabetes by the World Health Organization,
and polyphenolic compounds, phytosterols and the number of people suffering from diabetes has been
phytostanols, proteins, seven-carbon sugars, and 108 million in 1980 which has augmented to 422 million
vitamins (Table 1). The pharmacologically active in 2014 (Collaboration, NCDRF, 2016). Many studies
constituents of this plant have been also shown to have been accomplished on the antidiabetic effects of
possess antifungal, antiinflammatory, and antioxidant avocado in different experimental models (human,
activity in some studies (Lu et al., 2005; Sudhir, 2005). in vivo and in vitro) which are discussed in the
Furthermore, daily consumption of phytosterols and succeeding text (Table 2).

Table 1. The most abundant bioactive components of avocado

Categories Bioactive constituents References

Carotenoids Lutein, β-cryptoxanthin, zeaxanthin, α-carotene, and (Koh et al., 2004)


β-carotene
Fatty acids Monounsaturated (oleic and palmitic acids), unsaturated (Ozdemir and Topuz, 2004; Vekiari et al.,
(linoleic, palmitoleic, and linolenic acids) 2004)
Minerals Calcium, iron, magnesium, phosphorus, potassium, (Dreher and Davenport, 2013)
sodium, zinc, copper, manganese, and selenium
Phenolics and polyphenolic Phenolic acids (hydroxybenzoic and hydrocinnamic acids), (Golan et al., 1977; Kahn, 1983;
compounds flavonoids (rutin), stilbenes (resveratrol), coumarins, and Rodríguez-Carpena et al., 2011)
tannins (tannic acid)
Phytosterols and phytostanols β-sitosterol, campesterol, stigmasterol (Moghadasian and Frohlich, 1999;
β-sitostanol, campestanol, and stigmastanol Dreher and Davenport, 2013)
Proteins Asparagine, aspartic acid, glutamine, and glutamic acid (Ahmed and Barmore 1980)
Seven-carbon sugars D-mannoheptulose and perseitol (its reduced form polyol) (Liu et al., 1999)
Vitamins Vitamin A, vitamin B (B1, B2, B3, B5, B6, B12, folate, and (Dreher and Davenport, 2013)
choline), betaine, vitamin C, vitamin E (α-tocopherol,
β-tocopherol, γ-tocopherol, δ-tocopherol), and vitamin K1

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 821

Figure 1. Flow chart of systematic literature search showing the included and excluded studies.

Figure 2. The structural comparison of phytosterols, phytostanols, and cholesterol (the bioactive constituents of avocado).

Clinical studies for hypoglycemic effect by glycolysis decline via


hexokinase inhibition and weight control via appetite
In a randomized crossover study, 12 women with T2DM reduction (Sabaté et al., 2015). In addition, the results
received two different diets. One received a high of Wien et al. investigation on healthy overweight adults
monounsaturated fatty acids diet (including oleic acid showed that avocado in lunch meal attenuated the rise
from avocado and olive oil) and the other received in postprandial blood insulin levels 30 min after start
a high-complex carbohydrates diet for 4 weeks. of the lunch meal and diminished the desire to eat as
The results showed that the first diet maintained compared with the avocado-free control which could
an adequate glycemic control and offered a good be because of its anti-obesity effect (Wien et al., 2013).
management alternative (Lerman-Garber et al., 1994).
Another randomized clinical trial, investigated on 26
healthy overweight subjects, revealed that consumption In vivo studies
of half of a Hass avocado significantly reduced the blood
insulin and glucagon-like peptide-1 levels. It was Lima et al. investigated the hypoglycemic properties of
concluded that D-mannoheptulose may be responsible avocado and observed that oral administration of the
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
822 J. TABESHPOUR ET AL.

americana fruit (300 mg/kg, orally for 8 weeks) was


evaluated in SID rats. Body weight, serum levels of
insulin, hepatic, and skeletal muscle glycogen, activities
of hexokinase and glucose-6-phosphate dehydrogenase
enzymes in liver, kidney, skeletal muscle, and cardiac
muscle increased. While a significant decrease in FBG
levels, glycosylated Hb (which is one of the most
important indicators of diabetic condition) and the
reduced activities of aspartate transaminase (AST) and
alanine transaminase (ALT) enzymes in serum were
observed (Thenmozhi et al., 2012). The glucose
tolerance and insulin resistance reducing effects of
avocado oil were investigated in sucrose-induced
diabetic rats which can result from adding 5–20% of
avocado oil to the diet (Del Toro-Equihua et al., 2016).
Aqueous extract of avocado seed (300 and 600 mg/kg)
showed a significant reduction in BGLs, especially with
Figure 3. Some of pharmacologically active constituents of the higher dose, in alloxan-induced diabetic (AID) rats.
avocado. The histological investigation revealed a degenerative
effect on the pancreatic islet cells in diabetic rats which
hydroalcoholic extract of the leaves (0.15 and indicated that the aqueous extract of avocado seed had
0.3 g/kg/day, for 4 weeks) to streptozotocin-induced a protective effect on these cells. This study confirmed
diabetic (SID) rats, reduced blood glucose levels the significant hypoglycemic effect of avocado seed
(BGLs) while the metabolic state of the animals (Edem et al., 2009). The antidiabetic effect of the
improved. They proposed that the mechanism of this aqueous extract of avocado seed (400, 800 and
effect could be regulating the glucose uptake in liver 1200 mg/kg) was also investigated in AID rats and a
and muscles through Akt/PKB activation and significant decrease in FBG was observed (Alhassan
consequently restoring the intracellular energy balance et al., 2012).
(Lima et al., 2012). The SID rats which received The hypoglycemic and tissue-protective effects of the
ethanolic extract of P. americana fruit (300 mg/kg/day, hot-water extract of P. americana seeds (20, 30, 40 g/L,
orally for 4 weeks), showed a decrease in the raised for 3 weeks) were investigated in AID rats. It was shown
BGLs, glycosylated hemoglobin (Hb), blood urea, that the extract had a significant hypoglycaemic effect
and serum creatinine. It also increased the levels of and reversed the histopathological damage that
plasma insulin and Hb (Rao and Adinew, 2011). occurred in AID rats, comparable with the effects of
Streptozotocin-induced diabetic rats were orally treated glibenclamide (Ezejiofor et al., 2013b). Reduction in
with avocado oil (1 mL/250 g/day, for 3 months). oxidative stress, lipid peroxidation, and reactive oxygen
Avocado oil diminished reactive oxygen species levels, species production was observed in the liver
lipid peroxidation, oxidative stress, the activity of mitochondria of the SID rats which were treated with
complex III of the electron transport chain, and TG avocado oil (4 mL/kg) for 3 months. The oil also
levels in the brain while improved the reduced normalized the serum levels of cholesterol, TG, and
glutathione/oxidized glutathione ratio and brain induced weight gain. This study showed that avocado
mitochondrial function (Ortiz-Avila et al., 2015a). oil attenuated the harmful effects of diabetes on
Furthermore, the hypoglycemic activity of n-hexane oxidative condition of liver mitochondria (Ortiz-Avila
fraction from hydro-methanolic (2:3) extract of P. et al., 2015b). Antia et al. indicated that the aqueous leaf

Figure 4. Experimentally observed effects of different parts of avocado in respect of pharmacological actions. A: leaves. B: pulp. C: oil. D:
peel. E: seed. [Colour figure can be viewed at wileyonlinelibrary.com]

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 823

Table 2. Antidiabetic effects of avocado

Dosage (mg/kg/day)/
Part(s) of the plant Route/ duration Experimental
used/ Extract(s) Active constituents of treatment model Outcome Reference

Clinical trials

Oil/Avocado oil- MUFA (oleic acid) Not mentioned/p.o./ T2DM humans ↓FBG (Lerman-Garber et al.,
enhanced diet 4 weeks 1994)
Hass/Avocado oil- D-mannoheptulose 0.5 Hass avocado/p.o. Healthy overweight ↑Leptin (Sabaté et al., 2015)
enhanced diet /3 days humans ↓Blood insulin levels
↓GLP-1
Animal studies

Leaves/Hydroalcoholic flavonoids 150 and 300/p.o./ SID rats Activation of Akt/PKB (Lima et al., 2012)
4 weeks
Pulp/Ethanolic Fatty acids and 300/p.o./4 weeks SID rats ↑Plasma insulin (Rao and Adinew,
amino aids ↑Hb 2011)
↓BGLs and
Glycosylated Hb
↓Blood urea
↓Serum creatinine
↓AST, ALT and ALP
Oil/Not mentioned Carotenoids, 4 (mL/kg)/p.o./ SID rats ↑GSH/GSSG ratio (Ortiz-Avila et al.,
tocopherols, 3 months ↓ROS 2015a)
chlorophylls, ↓Complex III activity
vitamins, and oleic ↓TG
acid
Pulp/Hydro-methanolic Not mentioned 300/p.o./2 months SID rats ↑Body weight (Thenmozhi et al.,
↑Insulin and Glycogen 2012)
↑Hexokinase and
G6PD activities
↓FBG
↓Glycosylated Hb
↓AST and ALT
Oil/Avocado oil- MUFAs and PUFAs 5% (50 g oil + 950 g Sucrose-induced ↓Glucose tolerance (Del Toro-Equihua
enhanced diet feed diabetic rats ↓Insulin resistance et al., 2016)
pellets),10%,20%,
30%/p.o./2 months
Seeds/Aqueous Not mentioned 300 and 600/p.o./ AID rats ↓BGLs (Edem et al., 2009)
3 weeks
Seeds/Aqueous Flavonoids, minerals 400, 800, and 1200/p. AID rats ↓FBG (Alhassan et al.,
o./4 weeks 2012)
Seeds/Aqueous Flavonoids etc. 20, 30, 40 (g/L)/p.o. AID rats ↑Body weight (Ezejiofor et al.,
/3 weeks ↓FBG 2013b)
Oil/Avocado oil- Oleic acid 4 (mL/kg)/p.o./ SID rats ↑Body weight (Ortiz-Avila et al.,
enhanced diet 3 months ↓Oxidative stress 2015b)
↓Lipid peroxidation
↓ROS production
↓Cholesterol and TG
Leaves/Aqueous Saponins, tannins, 100, 150, and 200/p. AID rats ↓BGLs (Antia et al., 2005)
phlobatannins, o./1 week
flavonoids,
alkaloids, and
polysaccharides
Leaves/Ethanolic Not mentioned Not mentioned/p.o. SID rats ↑Hepatic glycogen (Gondwe et al., 2007)
/6 weeks ↓FBG
Seeds/Ethanolic Not mentioned 450 and 900/p.o./Not Normal and AID rats ↓BGLs (Edem, 2009)
mentioned
Leaves/Aqueous Not mentioned 10/p.o./10 weeks HCD rats ↓BGLs (Brai et al., 2007b)
and methanolic ↓TC
↓LDL-C

(Continues)

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
824 J. TABESHPOUR ET AL.

Table 2. (Continued)

Dosage (mg/kg/day)/
Part(s) of the plant Route/ duration Experimental
used/ Extract(s) Active constituents of treatment model Outcome Reference

In vitro studies

Leaves, peel, flesh, Bioactive phenolics 0–0.164, 0–0.4, Rat’s pancreas Inhibition of (Ajani and
and seeds/Aqueous 0–0.313 (mg/mL)/Not tissue homogenates α-amylase, Olanrewaju, 2014)
mentioned α-glucosidase
↓MDA
Leaves/Aqueous MUFAs Not mentioned/Not Gas Inhibition of (Uysal et al., 2015)
and methanolic mentioned chromatography α-amylase and
α-glucosidase
Leaves/Aqueous Tannins and 0.01–300(μg/mL)/Not PTP1B human Inhibition of PTP1B (Marrero-Faz et al.,
terpenoid glycosides mentioned recombinant 96 2014)
microplates

Abbreviations. MUFAs, monounsaturated fatty acids; p.o., oral route; T2DM, type 2 diabetes mellitus; FBG, fasting blood glucose; GLP-1,
glucagon-like peptide-1; SID, streptozotocin-induced diabetic; Akt/PKB, Akt/Protein Kinase B; Hb, hemoglobin; BGLs, blood glucose levels;
AST, aspartate transaminase; ALT, alanine transaminase; ALP, alkaline phosphatase; GSH/GSSG, reduced glutathione/oxidized glutathione;
ROS, reactive oxygen species; TG, triglyceride; G6PD, glucose-6-phosphate dehydrogenase; PUFAs, polyunsaturated fatty acids; AID,
alloxan-induced diabetic; HCD, high-cholesterol diet; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; MDA,
malondialdehyde; PTP1B, protein tyrosine phosphatase 1B.

extract of avocado (100, 150, and 200 mg/kg, for 1 week) be considered as a potential source for diabetes
significantly reduced the BGLs in AID rats (Antia et al., management (Uysal et al., 2015). The P. americana
2005). In a study, it was demonstrated that P. americana leaves were examined for protein tyrosine phosphatase
leaf ethanolic extracts exerted hypoglycemic effects via 1B inhibitory activity which is a relevant mechanism
increase in hepatic glycogen concentrations and involved in insulin resistance in T2DM. This inhibitory
decrease in FBG in a dose-dependent fashion in SID effect of the extract was concentration-dependent
rats (Gondwe et al., 2007). The effect of ethanolic seed (0.01–300 μg/mL) (Marrero-Faz et al., 2014). In another
extracts of P. americana at the doses of 450 and study, it was shown that avocado had a low glycemic
900 mg/kg on normal and AID rats was investigated in index, potent antioxidant activity, α-amylase and α-
another study. The extracts consumption significantly glucosidase inhibition activities, which can be the
reduced BGLs in AID rats in a dose-dependent manner possible mechanisms of avocado antidiabetic effects
and to a lesser extent in normal rats. This also confirms (Oboh et al., 2015). In an in vitro model, it was
the antidiabetic effect of this plant (Edem, 2009). The demonstrated that avocado affected the glucose
hypoglycemic and hypercholesterolemic (HCh) effect diffusion across the gastrointestinal tract and decreased
of P. americana leaf extracts (10 mg/kg, for 8 weeks) in vitro glucose movement more than 50% (Gallagher
were investigated in high-cholesterol diet (HCD) et al., 2003).
rats. Aqueous and methanolic extracts induced a In vitro studies, consistent with clinical and in vivo
decrease in total cholesterol (TC) and low-density experiments, revealed that avocado showed antidiabetic
lipoprotein cholesterol (LDL-C) while plasma HDL-C effects via regulating the glucose uptake in liver and
concentrations increased significantly. This could be an reducing glucose tolerance and insulin resistance.
alternative approach in the management of
atherosclerosis (Brai et al., 2007b).

In vitro studies EFFECT ON LIPID PROFILE

The antidiabetic effect of avocado was assessed in an Dyslipidemia is described as high levels of lipids
in vitro model of rat’s pancreas (tissue homogenates). (cholesterol, triglycerides, or both) carried by
The aqueous extracts of leaves, peel, flesh, and seed lipoproteins in the blood, and is a common risk factor
of avocado inhibited α-amylase (in the range of of CVDs (Miller, 2009). It is defined as high cholesterol
0–0.164 mg/mL), α-glucosidase (in the range of >200 mg/dL, low HDL < 40 mg/dL, and high
0–0.4 mg/mL), and the production of malondialdehyde TG ≥ 150 mg/dL (Fatema et al., 2016). More than 17
(MDA) (in the range of 0–0.313 mg/mL). They also million people die annually from CVDs. It is also
showed NO° and 2, 20 -azino-bis (3-ethylbenzthiazoline- estimated that by 2030, over 23 million people will
6-sulphonic acid) radical scavenging activity, which can die from CVDs each year (Mackay et al., 2004).
be considered as one of the possible mechanisms of The consumption of lipid-lowering medications may
T2DM management in a dose-dependent way (Ajani bring about some adverse effects (Hosseini and
and Olanrewaju, 2014). Besides, the methanolic and Hosseinzadeh, 2015). There is evidence that avocado
aqueous extracts of avocado leaves indicated α-amylase and some of its pharmacologically active constituents
and α-glucosidase inhibitory activities in an in vitro possess lipid-lowering and antihyperlipidemic effects
model. They showed that avocado leaves could (Table 3).
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
Table 3. Hypolipidemic effects of avocado

Part(s) of the plant used/ Dosage (mg/kg/day)/Route/


Extract(s) Active constituents duration of treatment Experimental model Outcome Reference

Clinical trials

Pulp/Not mentioned MUFAs 0.5 to 1.5 avocados/p.o. Humans HDL-C (no change) (Colquhoun et al., 1992)
/3 weeks Apo-A1 (no change)
↓TC
↓LDL-C
↓ApoB
Hass/Not mentioned MUFAs 136 g/p.o./5 weeks Obese or overweight humans (Wang et al., 2015)

Copyright © 2017 John Wiley & Sons, Ltd.


↓LDL particle number
↓small dense LDL-C
↓ratio of LDL/HDL
Avocado/Avocado-enriched MUFAs 75% avocado-derived MUFAs/p. Dyslipidemic patients ↑HDL-C (Carranza et al., 1995)
diet o./4 weeks ↓TG, TC, and LDL-C
Avocado/Avocado-enriched MUFAs 75% avocado-derived MUFAs/p. Healthy volunteers ↑HDL-C (Alvizouri-Muñoz et al., 1992)
diet o./2 weeks ↓TG, TC, and LDL-C
Avocado/Avocado-enriched MUFAs 2000 Kcal (lipids 53%, MUFAs Healthy normolipidemic ↓TG (López Ledesma et al., 1996)
diet 49 g, saturated/unsaturated volunteers and HCh patients ↓TC
ratio = 0.54)/p.o./one week ↓LDL-C
Avocado/Avocado-enriched MUFAs 75% avocado-derived MUFAs/p. Dyslipidemic patients ↓TG (Carranza-Madrigal et al., 1997)
diet o./4 weeks ↓LDL-C
Fruits/Avocado-enriched diet Fatty acids 0.5 to 1.5 avocados/p.o. Male patients ↓TC (Grant, 1960)
/8 weeks ↓Serum PLs
Avocado/Avocado-enriched Not mentioned 1 avocado (200 g)/p.o./6 weeks Overweight and obese ↓Body weight (Pieterse, 2003)
diet volunteers ↓BMI
↓Percentage body fat
Avocado and avocado oil/ Carotenoids 75 and 150 g avocados or 24 g Healthy volunteers ↑Absorption of lycopene, β- (Unlu et al., 2005)
Avocado-enriched diet avocado oil/p.o./8 weeks
AVOCADO AND METABOLIC SYNDROME

carotene α-carotene, and lutein


Animal studies

Avocado paste/Not mentioned Carotenoids, polyphenols, 2000/p.o./7 weeks HCD and high-fructose diet rats ↓TG, TC and LDL-C (Pahua-Ramos et al., 2014)
chlorophylls, and fiber ↓AST
↓ALT
Seeds/Ethanolic Not mentioned 450 and 900/p.o./2 weeks AID rats ↑HDL-C (Edem, 2010)
↓TG, TC, and LDL-C
Seed oil/Organic solvent Not mentioned 10%(w/w)/p.o./4 weeks Female rats ↓Total liver lipogenesis (Werman et al., 1991)
↓PLs and TG synthesis
↓Protein content of VLDL and
HDL-C fractions
Oil/Avocado oil-enhanced diet PUFAs, phytosterols, and Not mentioned/p.o./3 months Atherogenic-diet-fed rabbits ↑HDL-C (Kritchevsky et al., 2003)
carotenoids ↓TC
Oil/Avocado oil-enhanced diet HCD mice ↑HDL-C (Ortiz Moreno et al., 2007)

Phytother. Res. 31: 819–837 (2017)


825

(Continues)
Table 3. (Continued)
826

Part(s) of the plant used/ Dosage (mg/kg/day)/Route/


Extract(s) Active constituents duration of treatment Experimental model Outcome Reference

MUFAs,carotenoids, and 2.5% or 5% (g/100 g)/p.o./ ↓TG


phytosterols 4 weeks ↓AI
Fruits and seeds/Methanolic Phenolics, flavonoids, and 10%,20%,30%/p.o./6 weeks HCD rats ↑AI (Shehata and Soltan, 2013)
soluble dietary fiber ↑GSH
↓TC, TG, and LDL-C
↓AST and ALT
Seeds/methanolic and Saponins, flavonoids, and 125, 250, and 500/p.o. HFD rats ↓TC, LDL-C, and TG (Mfonobong et al., 2013)
petroleum ether phenols /4 weeks ↓Total lipids and PLs

Copyright © 2017 John Wiley & Sons, Ltd.


↓AI
Pulp/Hydroalcoholic Tocopherols, phytosterols, and 130 and 150/Stomach tube/ HCD rats ↑HDL-C (Elbadrawy and Shelbaya, 2013)
polyphenols 8 weeks ↓ALT and AST
↓Urea, creatinine, uric acid,
and bilirubin
↓Serum cholesterol, TG,
LDL-C, and VLDL-C
Pulp/Not mentioned Phytosterols, MUFAs, 1 and 2 (mL/rat/day)/p.o./ HCD rats ↓Serum cholesterol, LDL-C, (Al-Dosari, 2011)
carotenoids, and vitamins 10 weeks VLDL-C, and TG
↓GPT, GOT, GGT, and ALP
↓Bilirubin levels
↓Liver and heart MDA
Seed flour/Methanolic Phenolics and fiber 125, 250, and 500/Gavage/ HCD mice ↓TC and LDL-C (Pahua-Ramos et al., 2012)
2 weeks ↓AI
J. TABESHPOUR ET AL.

Fruit and leaves/ Not mentioned 300/p.o./Not mentioned Tyloxapol-induced ↓Serum cholesterol (Mahadeva Rao and Adinew,
Dichloromethanic and hyperlipidemic rats ↓TG 2011)
methanolic
Seeds/Ethanolic Saponins, flavonoids, and 10,20, and 40/p.o./2 weeks Hyperlipidemic rats ↓TC, TG, and LDL-C (Fidrianny et al., 2016)
tannins
Fruits/Hexane extract, Fatty acids (Avocado in diet = 1–5%), D-galactosamine-induced liver ↓ALT and AST (Kawagishi et al., 2001)
lyophilized, and powdered (Fractions = 4.4%; 0.53%; damage rats
avocado, different fractions 0.21%; 0.98%; and 1.8%)/p.o./
2 weeks
Leaves/Methanolic Flavonoids (luteolin, rutin, 20 and 40/p.o./8 weeks HCD rats ↑HDL-C (Kolawole et al., 2012)
quercetin, apigenin) ↓TC, TG, and LDL-C
Pulp/Ethanolic Saponins, flavonoids, and 300/p.o./4 weeks Nephropathy-induced HCD rats ↑SOD and CAT (Mahadeva Rao et al., 2014)
phytosterols ↑GPx, GST, GR, and GSH
↓TC and TG
↓Serum urea, creatinine, and
uric acid
↓TBARS and hydroperoxide
Up-regulated eNOS genes

Phytother. Res. 31: 819–837 (2017)


(Continues)
Table 3. (Continued)

Part(s) of the plant used/ Dosage (mg/kg/day)/Route/


Extract(s) Active constituents duration of treatment Experimental model Outcome Reference

Down-regulated iNOS genes


Seeds/Aqueous Phytosterols 100 and 200/p.o./8 weeks Rabbits ↓TC, TG, LDL-C, and total lipid (Nwaoguikpe and Braide, 2011)
Fruits/Avocado-enriched diet Phenolics and flavonoids 5,10, and 15% of dried CCL4-induced liver damage rats ↑SOD, GPx, and CAT (Mahmoed and Rezq, 2013)
avocado/p.o./8 weeks
Pulp/Avocado-enriched diet Fiber 230 g avocados/p.o./4 weeks HCD rats ↑Cecum weight (Naveh et al., 2002)
↓Food consumption
↓Body weight gain
↓Hepatic total fat

Copyright © 2017 John Wiley & Sons, Ltd.


Fruits/Hydroalcoholic MUFAs and vitamins 25,50,100, and 200/p.o./ Obesity-induced HFD rats ↑LPL (Monika and Geetha, 2016)
14 weeks ↓Blood and liver lipids
↓LPO
↓FASN
↓HMG CoA reductase
Fruits/Hydroalcoholic β-sitosterol, lutein,vitamins 100/p.o./14 weeks HFD rats ↑GSH (Padmanabhan and Arumugam,
A, C, and E ↑Adiponectin and mRNA 2014)
expression of adiponectin
↑PPAR-γ and protein expression
of PPAR-γ
↓BMI, TFP, and ADI
Leaves/Aqueous and MUFAs 10/p.o./8 weeks HFD rats ↓Body weight gain (Brai et al., 2007a, b)
methanolic ↓Liver weight
Fruits/hydroalcoholic Flavonoids, phenolics, and 100/p.o./14 weeks HFD male rats ↑Gene expression of FGF21 (Monika and Geetha, 2015)
phytosterols ↓BMI, TFP, and ADI
↓Blood cholesterol, TG, and LDL-
C
↓Leptin
AVOCADO AND METABOLIC SYNDROME

↓mRNA expression of FASN,


LPL, and leptin
Leaf/Aqueous and methanolic Flavonoids 10/p.o./8 weeks HFD rats ↑CAT, SOD, and GSH (Brai et al., 2012)
↓Protein carbonyl
↓Plasma MDA
In vitro studies

Leaves and fruit/Phenolic Phenolics 0–175(μg/mL)/Not mentioned Rat’s pancreas model ↓MDA (Oboh, 2014)

Abbreviations. MUFAs, monounsaturated fatty acids; p.o., oral route; HDL-C, high-density lipoprotein cholesterol; Apo-A1, apolipoprotein A1; TC, total cholesterol; LDL-C, low-density lipoprotein
cholesterol; ApoB, apolipoprotein B; TG, triglyceride; HCD, high-cholesterol diet; PLs, phospholipids; BMI, body mass index; AST, aspartate transaminase; ALT, alanine transaminase; AID, alloxan-
induced diabetic; VLDL, very-low-density lipoprotein; PUFAs, polyunsaturated fatty acids; AI, atherogenic index; HFD, high-fat diet; GPT, glutamic pyruvic transaminase; GOT, glutamic oxaloacetic
transaminase; GGT, γ-glutamyl transpeptidase; ALP, alkaline phosphatase; MDA, malondialdehyde; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GST, glutathione s-
transferase; GR, glutathione reductase; TBARS, thiobarbituric acid reactive substances; eNOS, endothelial nitric oxide synthase; iNOS, inducible nitric oxide synthase; CCL4, carbon tetrachloride;
LPL, lipoprotein lipase activity; LPO, lipid peroxides; FASN, fatty acid synthase; PPAR-γ, peroxisome proliferator-activated receptor-γ; FGF21, fibroblast growth factor-21; TFP, total fat pad mass;
ADI, adiposity index.

Phytother. Res. 31: 819–837 (2017)


827
828 J. TABESHPOUR ET AL.

Clinical studies significant increase in the percentage of plasma oleic


acid and a decrease in the percentage of myristic acid,
A randomized trial to evaluate the hypolipidemic effects body mass, body mass index (BMI), and the percentage
of avocado (between half and one and a half avocados of body fat, but TC, TG, LDL-C, HDL-C levels,
per day) was accomplished on 15 women lasting for fibrinogen, BP, and arterial compliance were not
3 weeks. A decrease in TC, LDL-C, and apolipoprotein changed significantly in the experimental group. This
B together with preservation of HDL-C and study concluded that intake of 200 g/day of avocado
apolipoprotein A-I was observed (Colquhoun et al., within an energy-restricted diet does not cause weight
1992). Also, in a crossover design, eight phenotype IV loss when substituted for 30 g of mixed dietary fat
and eight phenotype II dyslipidemic patients were (Pieterse et al., 2005).
examined for evaluation of the effect of avocado on
blood lipids. Patients received a rich-monounsaturated
fatty acids diet using the avocado as their major source In vivo studies
for 4 weeks in which 30% of the total calories were
consumed as fat and 75% of the total fat from avocado. The effect of reduced-calorie avocado paste (2 g/kg/day,
The results showed that the diet significantly decreased for 7 weeks) has been studied on HCD and high-
TC and LDL-C levels in phenotype II. On phenotype fructose diet rats. It showed a significant reduction in
IV, the diet produced a mild decrease in TG levels while TC, LDL-C, TG, AST, and ALT, and increased insulin
HDL-C significantly increased on both phenotypes sensitivity (Pahua-Ramos et al., 2014). The results of a
(Carranza et al., 1995). Sixteen healthy volunteers were study on AID rats suggested that ethanolic extracts of
evaluated for the effect of avocado on serum lipid levels. P. americana seed possess antihyperlipidemic effect at
The volunteers received a rich-monounsaturated fatty the doses of 450 and 900 mg/kg via a significant decrease
acids diet using the avocado as their major source for in the serum concentrations of TC, TG, and LDL-C, in
2 weeks in which 30% of the total calories were addition to a significant increase in the serum level of
consumed as fat and 75% of the total fat from avocado. HDL-C. The possible mechanism of this effect was
The results revealed that the diet lessened the serum mentioned to be controlling of the hydrolysis of certain
levels of TC, TG, and LDL-C while the level of HDL- lipoproteins and their selective uptake and metabolism
C increased. So, avocado can be used as an alternative by different tissues (Edem, 2010). Avocado-seed oil
to treat hyperlipidemia (Alvizouri-Muñoz et al., 1992). (10% w/w, orally for 4 weeks) showed a significant
Thirty healthy normolipidemic volunteers and 37 mild reduction in total liver lipogenesis, PL, and TG
HCh patients received an avocado-enriched diet (2000 synthesis, and protein content of plasma very-
Kcal, lipids 53% MFA 49 g saturated/unsaturated ratio low-density lipoprotein (VLDL) and HDL-C fractions
0.54) for 1 week. Both subjects revealed a significant in female rats. The possible mechanism for the
decrease in serum TC, LDL-C, and TG, and increase alternations in hepatic lipogenesis could be related to
in HDL-C levels with avocado diet. So avocado the marked proliferation of the smooth endoplasmic
is recommended for the treatment of HCh and reticulum which is known to be associated with
hypertriglyceridemic patients (López Ledesma et al., induction of enzymes involved in lipid biosynthesis
1996). A prospective, transversal, and comparative (Werman et al., 1991). The hypolipidemic and
study was accomplished on 13 patients with phenotype antiatherogenic effects of avocado oil were investigated
II dyslipidemia for 4 weeks. Their diet composed of in atherogenic-diet-fed rabbits. In this study, corn oil,
60% carbohydrates, 10% proteins, and 30% lipids, coconut oil, olive oil, and avocado oil were compared
75% of which was supplied by avocado. TG and for these effects. The results showed that the avocado
LDL-C decreased significantly. They concluded that oil, corn oil, and olive oil had the same effects.
avocado addition to a vegetarian diet does not But, the atheroma observed in the rabbits fed avocado
correct hypercholesterolemia unless lower amounts of oil was somewhat less severe than other oils
carbohydrates and polyunsaturated fatty acids are used (Kritchevsky et al., 2003). The hypolipidemic and
(Carranza-Madrigal et al., 1997). The effect of avocado antiatherogenic effects of avocado oil were evaluated
on serum cholesterol was investigated on 16 male on hypercholesterolemic-diet mice (2.5 or 5% g/100 g,
patients who consumed 0.5–1.5 avocados per day for for 4 weeks) and an increase in the HDL-C and
8 weeks. Total cholesterol (ester form free form) and maintenance in the concentration of the TG, in spite of
serum phospholipids (PLs) significantly declined at the the high caloric supply, was observed (Ortiz Moreno
endpoint (Grant, 1960). Furthermore, in a clinical et al., 2007).
study it was shown that addition of avocado or avocado The lowering effect of avocado seed on lipid profiles
oil to the vegetable-based diets of healthy volunteers in serum and liver was investigated in high-fat diet
enhanced the absorption of lycopene, β-carotene, (HFD) rats for 6 weeks. The results showed that
α-carotene, and lutein. It is concluded that adding both the fruit and the seed, especially the latter,
avocado fruit to carotenoid-containing foods can significantly decreased the serum levels of TC, TG,
facilitate carotenoid absorption (Unlu et al., 2005), and LDL-C, AST, and ALT activities, while the atherogenic
consequently aids to its lipid-lowering activity. index (=Serum TC  HDL-C/HDL-C) increased.
In a randomized, controlled, parallel study, 61 Furthermore, in the liver, the contents of TC and
free-living and energy-restricted-diets volunteers were TG decreased, and GSH increased. Consequently,
administered with 200 g/day of avocado (for 6 weeks) consuming avocado seed is recommended because it
which substituted for 30 g of other mixed dietary fats has strong antioxidant activity and improved lipid
such as margarine or oil, to investigate the possible profile (Shehata and Soltan, 2013). Petroleum ether
effects on weight loss, serum lipids, fibrinogen, and extracts of P. americana seeds were examined on HFD
vascular function. Although the results showed a rats. The extracts (125, 250, and 500 mg/kg/day, orally
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 829

for 4 weeks) significantly reduced the raised levels of of TC, TG, PLs, renal markers (serum urea, creatinine,
TC, LDL-C, TG, total lipids, total PLs, and the AI, and uric acid), and renal lipid peroxidation products
while increased HDL-C (Mfonobong et al., 2013). The such as thiobarbituric acid reactive substances and
results of a study on hydroalcoholic extract of avocado hydroperoxide noticeably decreased. Also, free radical
(130 and 150 mg/kg, via stomach tube for 8 weeks) on scavenging activity factors such as superoxide dismutase
HCD rats showed a significant reduction in serum (SOD), catalase (CAT), glutathione peroxidase (GPx),
ALT, AST, urea, creatinine, uric acid, and bilirubin glutathione s-transferase, and glutathione reductase
levels. Also, significant decreases in serum cholesterol, (GR) enzymes were significantly increased. The mRNA
TG, LDL-C, and VLDL-C were noted, while, the serum levels of endothelial nitric oxide synthase and inducible
level of HDL-C enhanced (Elbadrawy and Shelbaya, nitric oxide synthase genes were meaningfully up-
2013). P. americana pulp (1 and 2 mL/rat/day, orally regulated and down-regulated, respectively. This
for 10 weeks) showed a significant decrease in serum study demonstrated that avocado could be used as a
cholesterol, LDL-C, VLDL-C, TG, glutamic pyruvic nephroprotective agent via reducing the serum lipid
transaminase, glutamic oxaloacetic transaminase, γ- profile, renal oxidative stress, and regulating the
glutamyl transpeptidase, alkaline phosphatase (ALP), mRNA expression of NOS in renal artery (Mahadeva
bilirubin levels, liver, and heart MDA. There was also Rao et al., 2014).
a significant increase in non-protein sulfhydryl and TP The aqueous seed extract of P. americana, at doses of
contents in both tissues. These results suggested that 100 and 200 mg/kg/day for 2 months, was administered
avocado showed hypocholesterolemic and antioxidant to rabbits. The extract significantly and dose-
properties because of its phytoconstituents contents dependently showed reduction in TC, TG, LDL-C,
(Al-Dosari, 2011). Avocado seed flour (125, 250, and and the total lipid levels in the serum. Accordingly,
500 mg/kg/day, by gavage, for 2 weeks) was the seed of this plant could be a promising remedy for
administered to HCD mice. The results showed a the management of atherosclerosis, hypertension,
significant reduction in the levels of TC, LDL-C, and hyperlipidemia, hypercholesterolemia, and other
AI, suggesting the antioxidant and hypocholesterolemic abnormalities of lipid metabolism in humans
activity of this plant (Pahua-Ramos et al., 2012). (Nwaoguikpe and Braide, 2011). To assess the
The cholesterol-lowering activity of leaf hepatoprotective effect of avocado fruit, a rat model
(dichloromethanic and methanolic extracts) and fruit experimental study was accomplished in carbon
(dichloromethanic and methanolic extracts) of P. tetrachloride-induced liver damage rats which received
americana in tyloxapol-induced hyperlipidemic rats diets consist of 5, 10, and 15% dried avocado fruits for
were investigated [tyloxapol is used in Intraperitoneal 4 weeks. The results showed that avocado decreased
route injections to block plasma lipolytic activity, and serum concentrations of AST, ALT, ALP, TP, total and
thus the breakdown of TG-rich lipoproteins]. The direct bilirubin, and MDA while significantly increased
results showed that the extracts (300 mg/kg, orally and the activity of SOD, GPx, and CAT enzymes.
immediately after tyloxapol injection) could lower Accordingly, avocado fruit improved liver functions
cholesterol and TG levels in hyperlipidemic rats and showed antioxidant activity (Mahmoed and Rezq,
(Mahadeva Rao and Adinew, 2011). The ethanolic seed 2013). Avocado also revealed its lipid-lowering effect
extract of P. americana (10, 20, and 40 mg/kg/day, orally via influencing on endogenous fat synthesis and
for 2 weeks) was administered to hyperlipidemic male adiponectin formation through the transcription factor
Wistar rats. The results showed that the extract at the fibroblast growth factor-21 (Monika and Geetha,
dose of 10 mg/kg reduced TC and LDL-C and at the 2015). The leaf aqueous and methanolic extracts of P.
dose of 20 and 40 mg/kg reduced TG levels in serum. americana (10 mg/kg, for 8 weeks) were administered
This study showed that avocado can be served as a to HCh rats. A significant reduction in protein carbonyl
potential medicinal plant to lower serum lipid levels and plasma MDA showed that the extract lowered the
and subsequently the risk of CVDs (Fidrianny et al., oxidative stress. Besides, an increase in the activities of
2016). A rat model of D-galactosamine-induced liver CAT and SOD as well as reduced GSH was observed.
damage was conducted to assess the protective effects The aforementioned effects demonstrated that the
of 22 fruits against liver injury (four experiments with extract could be used in the management of diseases
lyophilized and powdered avocado, its different associated with hyperlipidemia (Brai et al., 2012).
fractions and hexane extract) for 2 weeks. Among Conversely, in a study, the effect of dietary
different fruits, avocado showed extraordinarily potent consumption of avocado oil was conducted on sucrose-
liver injury suppressing effect, dose dependently fed rats. No changes in biochemical markers including
(Kawagishi et al., 2001). The leaf extract of P. americana glucose, TC, TG, total protein, albumin, globulin, direct
(20 and 40 mg/kg/day for 8 weeks) was administered bilirubin, glutamic pyruvic transaminase, glutamic
to HCD rats. The results indicated that this extract, oxaloacetic transaminase, ALP, cholinesterase, and
in a dose-dependent manner, significantly reduced α-amylase were found while body weight gain was
the plasma levels of TC, TG, and LDL-C and observed in the rats (Carvajal-Zarrabal et al., 2014b).
increased HDL-C levels. The extracts also caused
significant reduction of plasma lipid peroxidation.
In this study, the antihyperlipidemic effect of In vitro studies
avocado was comparable with that of cholestyramine
(Kolawole et al., 2012). The effects of avocado pulp The inhibitory effect of the phenolic extract of the
(300 mg/kg/day, orally for 4 weeks) on biochemical, leaves, seed, and fruit of P. americana (0–175 μg/mL)
histological, and gene expression were investigated in on Fe2+-induced lipid peroxidation in rat’s pancreas
hypercholesterolemic-diet-fed nephropathy induced was examined in vitro. The results showed a significant
albino rats. Via administration of the extract, the levels decrease in the MDA level in a dose-dependent
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
830 J. TABESHPOUR ET AL.

manner. The seed extract have the highest inhibitory (25, 50, 100, and 200 mg/kg) on obesity-induced HFD
effect. The possible mechanism is probably via the rats were investigated for 14 weeks. The experiment
ability of the extracts on chelating Fe2+ and scavenging showed a significant decrease in blood and liver lipids,
free radicals (Oboh, 2014). LPO, the activity of lipid metabolic key enzymes
Aforementioned experimental studies showed that such as fatty acid synthase (FASN) and HMG CoA
avocado had promising effects on abnormal lipid profile reductase in liver, while the antioxidant status and
via different mechanisms including increase in free lipoprotein lipase (LPL) activity increased. The possible
radical scavenging activity factors such as SOD, CAT, mechanism was probably via modulating the activities of
GPx, glutathione s-transferase, and GR enzymes; FASN and HMG CoA reductase in the liver (Monika
improving serum lipid biomarkers such as TC, TG, and Geetha, 2016).
LDL-C, and HDL-C; regulating the hydrolysis of For us to examine the hypolipidemic and anti-obesity
different lipoproteins and their selective uptake and effects of hydroalcoholic fruit extract of P. americana,
metabolism by different tissues; decrease in liver HFD rats were administered with the dose of
lipogenesis and oxidative stress. 100 mg/kg/day of the extract orally for 14 weeks. The
results revealed a significant decrease in BMI, total
fat pad mass (TFP), and adiposity index (ADI).
Although, an increase was observed in the levels of
EFFECT ON OBESITY GSH, adiponectin, mRNA expression of adiponectin,
peroxisome proliferator-activated receptor-γ (PPAR-γ),
Obesity which is associated with dyslipidemia, is a and protein expression of PPAR-γ. Finally, it is
critical global issue described by additional fat content concluded that avocado possesses hypolipidemic and
in adipose tissue as a result of unhealthy dietary habits anti-obesity activity probably via increasing the mRNA
causing negative energy balance (Monika and Geetha, expression of adiponectin and PPAR-γ, which can
2016; Colquhoun et al., 1992). According to the reduce the risk of hyperlipidemia and obesity
McKinsey Global Institute report, more than 2.1 billion (Padmanabhan and Arumugam, 2014). The effect of
people (nearly 30% of the world population) are aqueous and methanolic leaf extracts of P. americana
overweight or obese. It is estimated that by 2030 it will (10 mg/kg/day) on body weight and liver lipids in
rise to 41% (Carranza et al., 1995). Several methods HCD rats were investigated for 8 weeks, resulting in
are available to prevent obesity such as working out, 14% and 25% reduction in the body weight gain,
applying medication, and modifying the regimen along respectively. The methanolic extract also provoked a
with avocado which has shown promising anti-obesity minimal (8%) reduction in mean liver weight. It could
effect in different studies. be concluded that the leaf extract of avocado increased
catabolism of lipids accumulated in adipose tissue
causing a reduction in body weight but did not influence
Clinical studies liver lipid levels in rats (Brai et al., 2012). High-fat diet
rats were treated with 100 mg/kg of hydroalcoholic fruit
In a randomized, crossover, controlled feeding trial, extract of avocado for 16 weeks. There was a significant
performed on 45 overweight or obese participants, the reduction in BMI, ADI, TFP, blood cholesterol, TG,
hypolipidemic effect and also the effect of avocado LDL-C, and leptin as well as the mRNA expression of
consumption (136 g of Hass avocado per day) on CVD FASN, LPL, and leptin in subcutaneous and visceral
risk factors were investigated. The results indicated that adipose tissue while the gene expression of fibroblast
avocado significantly decreased LDL particle number, growth factor-21 significantly increased. The current
small dense LDL-C, and the ratio of LDL/HDL from study concluded that the anti-obesity effect of avocado
baseline, and showed beneficial effects on cardio- was due to its significant effect on leptin activity which
metabolic risk factors (Carranza et al., 1995). A is responsible for satiety and hunger to control the food
controlled parallel intervention study was accomplished intake (Monika and Geetha, 2015).
on overweight and obese volunteers with BMI of Several studies have demonstrated the anti-obesity
27–44 kg/m2, to evaluate the effect of avocado (one effect of avocado via different proposed mechanisms
avocado/day for 6 weeks) on weight loss and serum such as increase in the mRNA expression of adiponectin
lipids. Significant reductions in body weight, BMI, and and PPAR-γ; increase in catabolism of lipids
percentage of body fat were observed (Unlu et al., accumulated in adipose tissue; reduction in BMI, body
2005). weight, ADI, TFP, blood cholesterol, TG, LDL-C, and
leptin as well as the mRNA expression of FASN, LPL,
and leptin in subcutaneous and visceral adipose tissue;
In vivo studies and diminution of oxidative stress.

The effect of avocado pulp (230 g avocado) on body


weight was investigated in HCD rats for 4 weeks. The
results showed that food consumption, body weight EFFECT ON HIGH BLOOD PRESSURE
gain, and hepatic total fat levels were lower while the
cecum weight was higher in avocado-fed rats. In this Hypertension is estimated to cause 7.5 million deaths,
study, it was concluded that an appetite depressant is about 12.8% of the total of all deaths, worldwide, and
present in avocado and that avocado pulp interferes is a major risk factor for coronary heart disease,
with hepatic fat metabolism (Monika and Geetha, hemorrhagic stroke, ischemic, and premature deaths.
2015). The hypolipidemic and body weight-lowering Furthermore, hypertension accompanies with some
effects of hydroalcoholic fruit extract of P. americana complications including heart failure, peripheral
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 831

vascular disease, retinal hemorrhage, and renal and potassium, sodium, and albumin, while the levels of
visual impairments (Papathanasiou et al., 2015). This HDL-C, GSH, nitrites, and the activities of SOD and
pervasive disease is defined as an average systolic blood CAT increased. It can be concluded that the extract
pressure ≥ 140 mmHg or an average diastolic blood showed antihypertensive activity (Dzeufiet et al.,
pressure ≥ 90 mm (CDC, 2012). Although the 2014). The BP response to angiotensin II and the fatty
antihypertensive drugs such as thiazides, angiotensin acid composition of cardiac and renal membranes were
converting enzyme inhibitors, beta-blockers, and evaluated with avocado oil-enhanced diet (10% w/w
calcium channel blockers reduce the risk of mortality, for 2 weeks) in rats. Avocado oil increased the oleic acid
stroke, coronary heart disease, and/or CVDs, but content of the cardiac membrane while it decreased the
adverse events and the complexity of such agents tend α-linolenic acid and increased the arachidonic acid
to decrease treatment adherence. Therefore, content of the kidney membrane. The results showed
complementary and herbal medicines are gaining that this diet was able to modify the fatty acid content
increasing popularity among patients with the risk of in the mentioned membranes in a tissue-specific
CVDs, and there is a need to explore the medicinal manner. The rise in renal arachidonic acid suggested
plants having very low adverse effects for the treatment that diet content could be an important factor in
of hypertension (Xiong et al., 2015). There are several vascular responses, and the desired effects for the
clinical and experimental studies which confirm the use cardiovascular system could not be ascribed to the
of avocado as a remedy for hypertension (Table 4). components of the oil and proposed that other active
constituents present in avocado fruit and leaves might
be involved (Salazar et al., 2005). The aqueous seed
Clinical studies extract of P. americana (200, 500, and 700 mg/kg/day,
for 4 weeks) were used to assess its antihypertensive
For us to assess the effect of liquid extract of avocado and antihepatotoxic effect. The results showed that the
leaf on the plasma levels of LDL-C, TC, ALT, and extract significantly lowered the weight gain, BP, and
AST, 50 newly-diagnosed hypertensive patients with ALP activity at all dose levels. The levels of protein,
an abnormal increase in plasma cholesterol and BP albumin, ALT, and AST showed no significant change.
were treated with 60 mL/day of the extract. The results Conclusively, avocado seeds could be used as an
revealed a significant reduction in the plasma levels of antihypertensive agent and also showed antihepatotoxic
LDL-C and TC, and increase in ALT and AST in the activity (Imafidon, 2010). The aqueous extract of
subjects. It can be concluded that although this extract the leaves and seeds of P. americana (2 mL) was
can induce hepatotoxicity, but also it can be used in investigated on the enzyme activities of blood and liver
the treatment of hypertension (Olaniyan, 2014). of the rats. The results showed a significant decrease
and increase in the activities of ALP, ALT, AST, and
acid phosphatase in the liver and plasma of the rats,
In vivo studies respectively; which indicated a probable damage to the
hepatic cells and might be as a result of prolonged
For is to investigate the hypotensive effect of aqueous usage (1, 2, 3, 4, and 5 days) of the extract. The
seed extract of P. americana, normotensive rats were cholesterol levels also decreased which indicated the
treated with 240, 260, 280 mg/kg/day of the extract. hypocholesterolimic effect of avocado and it might be
Treatment of the rats for 10 days showed a significant helpful in the management of hypertension and
decrease in mean arterial blood pressure and heart reducing the risk of CVDs (Oyeyemi and Oyeyemi,
rate (HR) which were comparable with those of 2015).
acetylcholine (Anaka et al., 2009). Hypertensive rats
were treated with 200, 500, and 700 mg/kg of the
aqueous seed extract of P. americana for 4 weeks to In vitro studies
evaluate the effect of this plant on BP and lipid profile.
The extract at the dose of 500 mg/kg showed a The antioxidant activity of ripe and unripe avocado was
significant reduction in BP as well as TC, LDL-C, TG investigated via analysis of the minerals content using l,
levels in the plasma, kidney, liver, and heart. It can be l-diphenyl, 2-picrylhydrazyl (DPPH), superoxide, and
concluded that treatment with the dose of 500 mg/kg hydrogen peroxide scavenging assays. The results
of the seed extract of this plant not only lowers the BP showed that the content of sodium, calcium, magnesium,
but also may produce a favorable lipid profile (Imafidon iron, and manganese was higher in ripe avocado seeds,
and Amaechina, 2010). Methanolic and aqueous leaves while the content of potassium and zinc were higher in
extracts of P. americana were administered to unripe avocado seeds. It could be perceived that firstly,
normotensive rats (6.25, 12.5, 25 and 50 mg/kg, for the seeds from both ripe and unripe avocado contained
2 weeks). The intravenous route injection of the extracts significant antioxidant activities; secondly, the seeds
showed a significant reduction in mean arterial blood from unripe avocado, being rich in potassium compared
pressure (Adeboye et al., 1999). to sodium, could be used in the management of
The antihypertensive effect of the aqueous extract hypertension (Alagbaoso et al., 2015). The aqueous
obtained from the mixture of fresh leaf of P. americana, extract of leaves and seeds of avocado (50 μL) were
stems, and fresh leaf of Cymbopogon citratus, fruits of used to investigate for their possible inhibitory effect
Citrus medica and honey (50, 100, and 150 mg/kg/day on angiotensin 1 converting enzyme (A1CE) activity
for 5 weeks) on ethanol-and sucrose-induced in vitro. The results showed that the leaf extract have
hypertension in rats were evaluated. The extract caused significantly higher total phenol, flavonoid content,
reduction in BP, HR, MDA, the levels of TC, LDL-C, and antioxidant properties than the seed extract, while,
TG, AI, glucose, proteins, AST, ALT, creatinin, the seed extract have higher inhibitory effect on A1CE
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
Table 4. Hypotensive effects of avocado
832

Clinical trials

60(mL/day)/p.o./Not Newly diagnosed ↑ALT and AST


Leaves/Liquid Alkaloids mentioned hypertensive patients ↓TC and LDL-C (Olaniyan, 2014)

Animal studies

Seed/Aqueous Tannins 240,260, and 280/i.v./10 days Normotensive rats ↓MABP (Anaka et al., 2009)
↓HR
Seed/Aqueous Potassium MUFAs, carotenoids, 200,500, and 700/i.v./4 weeks Hypertensive rats ↓BP (Imafidon and Amaechina,
and β-sitosterol ↓TC, TG, and LDL-C 2010)
Leaves/Aqueous and Alkaloids, saponins, flavonoids, 6.25,12.5,25, and 50/i.v./ Normotensive rats ↓MABP (Adeboye et al., 1999)

Copyright © 2017 John Wiley & Sons, Ltd.


methanolic and tannins 2 weeks
Leaves/Aqueous Flavonoids, saponins, tannins, 50,100, and 150/p.o./5 weeks Ethanol-and sucrose-induced ↑HDL-C (Dzeufiet et al., 2014)
polyphenols, and alkaloids hypertensive rats ↑GSH, nitrites, SOD, and CAT
↓BP and HR
↓MDA
↓TC, LDL-C, and TG
↓AI
↓Glucose and proteins
↓AST and ALT
↓Creatinin, potassium, sodium,
and albumin
Oil/Avocado oil-enhanced Not mentioned 10% (w/w)/p.o./2 weeks Male rats ↑Cardiac oleic acid (Salazar et al., 2005)
diet ↑Kidney arachidonic acid
↓Kidney α-linolenic acid
J. TABESHPOUR ET AL.

Seeds/Aqueous Not mentioned 200,500, and 700/p.o./ Hypertensive and ↓Weight gain (Imafidon, 2010)
4 weeks normotensive rats ↓BP
↓ALP
Leaves and seeds/Aqueous Not mentioned 2 mL/p.o./5 days Rats Plasma: ↑ALP, ALT, AST, and (Oyeyemi and Oyeyemi,
ACP 2015)
Liver: ↓ALP, ALT, AST, and ACP
In vitro studies

Seeds/Not mentioned Potassium and phenolics Not mentioned/Not mentioned DPPH, superoxide, and ↓BP (Alagbaoso et al., 2015)
hydrogen peroxide
scavenging assays
Leaves and seeds/Aqueous Phenolics and flavonoid 5 μL/Not mentioned Spectrophotometery Inhibition of A1CE (Odubanjo et al., 2016)
A1CE inhibition assay
Leaves/Aqueous Not mentioned 0.01–12.8(mg/mL)/Not Isolated rat aorta Inhibition of Ca2+ influx through (Owolabi et al., 2005)
mentioned calcium and receptor-operated
channels

Abbreviations. p.o., oral route; ALT, alanine transaminase; AST, aspartate transaminase; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; i.v., intravenous route; MABP, mean arterial
blood pressure; HR, heart rate; MUFAs, monounsaturated fatty acids; BP, blood pressure; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; SOD, superoxide dismutase; CAT, catalase;
MDA, malondialdehyde; AI, atherogenic index; ALP, alkaline phosphatase; ACP, acid phosphatase; DPPH, l; l-diphenyl; 2-picrylhydrazyl; A1CE, angiotensin 1 converting enzyme.

Phytother. Res. 31: 819–837 (2017)


AVOCADO AND METABOLIC SYNDROME 833

than the leaf extract. It could be concluded that the seed The results indicated that the extract caused
indicated a better antihypertensive activity while the bradycardia, vasorelaxation, and hypotension in these
leaf revealed a better antioxidant activity (Odubanjo animal models, which encouraged the use of avocado
et al., 2016). The vasorelaxant effect of the aqueous in management of essential hypertension and certain
leaves extract of P. americana (0.01–12.8 mg/mL) was cases of cardiac dysfunctions (Ojewole et al., 2007).
examined on isolated rat aorta. The results indicated The effect of methanolic seed extracts of P. americana
that the extract showed a significant vasorelaxation in (200, 400, 800, and 1600 mg/kg/day for 4 weeks) on
a concentration-related manner, and the effect was prothrombin time (PT) and activated partial
dependent on the synthesis or release of endothelium- thromboplastin time (APTT) tests was evaluated in
derived relaxing factors and the release of prostanoid. mice. The results showed that the increase in PT and
This effect could also be probably due to inhibiting APTT was dose dependent. Because the extract showed
Ca2+ influx through calcium channels and, to a lesser anticoagulant activity as it prolonged PT and APTT, it
extent, receptor-operated channels. It could be could be used as a cardio protective agent (EE et al.,
concluded that mentioned vascular effects could explain 2015). The antiplatelet and antithrombotic activities of
the hypotensive activity of the extract and its usage avocado pulp were investigated both in vitro and
in the treatment of hypertension (Owolabi et al., 2005). in vivo. The results showed that antiplatelet activity
The vasorelaxant effect of avocado has been was initially attributed to Persenone-C (the most potent
demonstrated to be via the synthesis or release of antiplatelet acetogenin) and Persenone-A (in vitro).
endothelium-derived relaxing factors, the release of The latter showed protective effects against arterial
prostanoid and inhibiting Ca2+ influx through calcium thrombosis (25 mg/kg, in vivo) as increased coagulation
channels. times and decreased thrombus formation. Inhibition of
platelet aggregation may be due to the existence of
acetogenin compounds in avocado. These compounds
showed potential preventive effect on thrombus
EFFECT ON ATHEROSCLEROSIS formation and were effective in ischaemic diseases
(Rodriguez-Sanchez et al., 2015). Avocado fruit extracts
Clinical studies were examined for their phytochemical, toxicological,
biochemical, and hematological properties in rats.
Postprandial effect of 68 g addition of avocado to a Extract treatment caused reduction of the activity of
hamburger was evaluated on vasodilation and liver and heart enzymes including TC, VLDL, LDL,
inflammation of healthy volunteers. The while HDL levels increased PT and APTT with kaolin
vasoconstriction following hamburger ingestion was also decreased. It could be concluded that the extract
not observed when the avocado flesh was ingested acted as a potential inhibitor of CVDs because of its
together with the burger. There was a significant preventive and possible curative values. Its role in the
preservation of Ikappa-B alpha as an inflammatory regulation of blood clotting time may be because of
factor, consistent with reduced activation of the its significant vitamin K content (Gouegni and
NF-kappa B inflammatory pathway. Avocado also Abubakar, 2013).
decreased the elevated levels of TG. The results
suggested that avocado had beneficial anti-
inflammatory and vascular health effects when
co-ingested with a hamburger patty (Li et al., 2013).
ANTIOXIDANT ACTIVITY

In vivo studies Different parts of avocado such as leaves, pulp, seeds,


peels, roots, and plant derived products are proved to
Cardiovascular risk profile markers were evaluated in a have significant health benefits in different components
rat model of sucrose-indused methabolic changes, of MetS because of their antioxidant activity, which can
treated with avocado oil. The oil reduced TG, VLDL, neutralize the oxidative stress, and cellular oxidation
and LDL (significant) levels while no change was reaction under appropriate conditions (Abdulazeez
observed in HDL levels. It also reduced the and Ponnusamy, 2016; Wang et al., 2016). Promising
concentration of high sensitivity C-reactive protein observations have been made on the andioxidant
which is an indicator of inflammatory processes. The activity of avocado and its antidiabetic effect via
results of this study showed that avocado oil different mechanisms such as inhibition of α-amylase
consumption reduced inflammatory processes and via and α-glucosidase (Ajani and Olanrewaju, 2014). Also
improving these biomarkers, could prevent the the hypolipidemic effect of avocado has been
development of MetS (Carvajal-Zarrabal et al., 2014a). demonstrated to be through its antioxidant activity
The cardiovascular effects of P. americana aqueous leaf because of its high carotenoid content (Unlu et al.,
extract were investigated in three different animal 2005). The hypotensive effect of avocado and its
models. In the first experiment, the effect of the extract antioxidant activity has been proved via the
on myocardial contractile performance was assessed on improvement of biochemical and oxidative status, and
guinea pig isolated atrial muscle strips. In the second via protecting liver, kidney, and vascular endothelium
experiment, the vasodilatory effects of the extract were against oxidative stress parameters (Dzeufiet et al.,
assessed on isolated portal veins and thoracic aortic 2014). It is also believed that avocado in the diet
rings of healthy rats in vitro. In the third experiment, through its effects on lipid metabolism and antioxidant
the hypotensive effect of the extract was assessed in properties, plays an important role in the prevention of
healthy normotensive and hypertensive rats in vivo. CVDs (Pieterse, 2003).
Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
834 J. TABESHPOUR ET AL.

For us to examine the antioxidant activity of the were useful for future antioxidant products (Kumar and
solvent extracts of avocado seeds, four different Cumbal, 2016).
fractions were used to calculate this activity. All
fractions were able to scavenge DPPH among which
one fraction had antioxidant activity comparable with
ascorbic acid (Nagaraj et al., 2010). Furthermore, the SAFETY
seeds, peels, and pulp of avocado were extracted with
acetone/water/acetic acid solvents to determine their The safety of avocado has been demonstrated in a study
antioxidant capacity (1 g of pulp or 0.5 g of seeds or in which 2.5 g/kg (p.o) per day of the aqueous seed
peels were extracted in 10 mL of the solvents), total extract of P. americana, in a sub-acute experiment, were
phenolic content and to identify the major antioxidant administered to the rats for 4 weeks. The extract did not
compounds. Among different parts, the seeds showed affect the whole body weight or organ-to-body weight
the highest antioxidant capacity. Procyanidins were ratios though significantly increased the fluid intake
the major phenolic compounds that contributed to and the concentration of total proteins. It could be
antioxidant capacity. This study suggested that avocado concluded that this extract at the mentioned dose was
seeds and peels could be used as source of antioxidants safe on sub-acute basis (Ozolua et al., 2009).
(Wang et al., 2010). The anticholinesterases and
antioxidant activities of P. americana leaf and seed
aqueous extracts were investigated via the activities
of acetylcholinesterase and butyrylcholinesterase CONCLUSION
enzymes which are linked with Alzheimer disease, and
DPPH, hydroxyl and nitric oxide scavenging ability, In this review, we summarized different in vivo, in vitro
respectively. The leaf extract showed the highest and clinical studies accomplished by researchers around
phenolic content and radical scavenging activity (Oboh the world to find out the role of peel, seed, flesh, and
et al., 2016). Different phytoconstituents of the leaves of leaves of avocado in MetS. Most of these studies have
P. americana were isolated, and their antioxidant suggested the use of this plant in the diet, on a daily
activity were evaluated using DPPH and H2O2 assays. basis, to manage different components of MetS.
This study concluded that the leaves had antioxidant According to the experimental studies reported in the
activity which may be helpful in preventing the progress literature, we observed that avocado had the most effect
of various oxidative stress related diseases (Owolabi on lipid profile. The most affected biomarkers were
et al., 2010). Different phytoconstituents of the leaves LDL-C, HDL-C, TG, TC, and PLs. The reported
of P. americana were isolated and their antioxidant mechanism of this effect was regulating of the hydrolysis
activity were evaluated using DPPH, NO and reducing of certain lipoproteins and their selective uptake and
power and radical scavenging activity assays. This study metabolism by different tissues such as liver and
concluded that methanolic extract of avocado pancreas. Another possible mechanism could be related
possessed significant antioxidant activity (Asaolu to the marked proliferation of the liver smooth
et al., 2010). In a study, it was shown that avocado fruit endoplasmic reticulum which is known to be associated
had great ascorbic acid, total phenol concentrations, with induction of enzymes involved in lipid biosynthesis.
antioxidant capacity, and high levels of catalase, In this review article, satisfactory clinical evidence
ascorbate peroxidase, and GR activities (Wang et al., suggested that avocado can be used as herbal dietary
2016). The diethyl nitrosamine-induced elevated levels supplements for treatment of different components of
of tumor necrosis factor-α, cyclooxygenase-2, MetS. Although, avocado like other herbal products is
lipoxygenase, caspase-3, DNA fragmentation, NO, safe and generally better tolerated than synthetic
MDA, TP, and serum lipid profile and liver functions medications, there is limited scientific evidence to
were corrected in rats treated with avocado extract evaluate different side effects because of contaminants,
(1 mL/kg/day, orally for 4 weeks). The results indicated or interactions with drugs. Besides, further studies need
that avocado was able to diminish oxidative stress, to be accomplished on the metabolic effects of different
inflammation, and apoptosis induced by diethyl parts of avocado for other possible mechanisms.
nitrosamine (Hamouda, 2015). In a study, the
antioxidant activity of avocado was shown in different
parts as follows: leaf > peel > oil > pulp, using DPPH Conflict of Interest
assay. The antioxidant activity showed a positive
correlation with total flavonoid content, and these parts The authors declare not to have any conflicts of interest.

REFERENCES
Abdulazeez SS, Ponnusamy P. 2016. Antioxidant and Akaberi M, Hosseinzadeh H. 2016. Grapes (Vitis vinifera) as a
hypoglycemic activity of strawberry fruit extracts against potential candidate for the therapy of the metabolic syndrome.
alloxan induced diabetes in rats. Pak J Pharm Sci 29: 255–260. Phytother Res 30: 540–556.
Adeboye JO, Fajonyomi MO, Makinde JM, Taiwo OB. 1999. A Al-Dosari MS. 2011. Hypolipidemic and antioxidant activities of
preliminary study on the hypotensive activity of Persea avocado fruit pulp on high cholesterol fed diet in rats. Afr J
americana leaf extracts in anaesthetized normotensive rats. Pharm Pharmacol 5: 1475–1483.
Fitoterapia 70: 15–20. Alagbaoso CA, Tokunbo II, Osakwe OS. 2015. Comparative
Ajani A, Olanrewaju BO. 2014. Avocado pear fruits and leaves study of antioxidant activity and mineral composition of
aqueous extracts inhibit α-amylase, α-glucosidase and snp methanol extract of seeds of ripe and unripe avocado
induced lipid peroxidation–an insight into mechanisms involve pear (Persea americana, Mill.). NISEB Journal 15:
in management of type 2 diabetes. Int J Appl Nat Sci 3: 21–34. 123–127.

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 835

Alhassan A, Sule M, Atiku M, Wudil A, Abubakar H, Mohammed S. of Citrus medical L. (Rutaceae) as well as honey in ethanol and
2012. Effects of aqueous avocado pear (Persea americana) sucrose experimental model. BMC Complement Altern Med
seed extract on alloxan induced diabetes rats. Greener J Med 14: 507.
Sci 2: 5–11. Edem D. 2009. Hypoglycemic effects of ethanolic extracts of
Alvizouri-Muñoz M, Carranza-Madrigal J, Herrera-Abarca JE, Alligator Pear Seed (Persea americana Mill) in rats. Eur J Sci
Chávez-Carbajal F, Amezcua-Gastelum JL. 1992. Effects of Res 33: 669–678.
avocado as a source of monounsaturated fatty acids on Edem D, Ekanem I, Ebong P. 2009. Effect of aqueous extracts of
plasma lipid levels. Arch Med Res 23: 163–167. alligator pear seed (Persea americana mill) on blood glucose
Anaka ON, Ozolua RI, Okpo SO. 2009. Effect of the aqueous seed and histopathology of pancreas in alloxan-induced diabetic
extract of Persea americana Mill (Lauraceae) on the blood rats. Pak J Pharm Sci 22: 272–276.
pressure of Sprague-Dawley rats. Afr J Pharm Pharmacol 3: Edem D. 2010. Antihyperlipidemic effects of ethanolic extracts of
485–490. alligator pear seed (persea america a mill) in alloxan-induced
Antia B, Okokon J, Okon P. 2005. Hypoglycemic activity of diabetic rats. Pharmacologyonline 1: 901–908.
aqueous leaf extract of Persea americana Mill. Indian J Ee N, Ufelle S, Anele T. 2015. Effect of methanolic seed extract of
Pharmacol 37: 325–326. (avocado pear) on prothrombin time and activated partial
Asaolu M, Asaolu S, Fakunle J, Emman-Okon B, Ajayi E, Togun R. thromboplastin time in mice. J Exp Res 3: 92–96.
2010. Evaluation of in-vitro antioxidant activities of methanol Elbadrawy E, Shelbaya L. 2013. Hypolipidemic activities of
extracts of Persea americana and Cnidoscolus aconitifolius. hydroalcoholic extract of avocado fruit on high cholesterol
Pak J Nutr 9: 1074–1077. fed diet in rats and its antioxidant effect in vitro. J Am Sci 9:
Awad AB, Fink CS. 2000. Phytosterols as anticancer dietary 337–343.
components: evidence and mechanism of action. J Nutr 130: Ezejiofor AN, Okorie A, Orisakwe OE. 2013a. Hypoglycaemic and
2127–2130. tissue-protective effects of the aqueous extract of Persea
Brahmachari G. 2011. Bio-flavonoids with promising antidiabetic americana seeds on alloxan-induced albino rats. Malays J
potentials: a critical survey. In Opportunity, Challenge and Med Sci 20: 31–39.
Scope of Natural Products in Medicinal Chemistry, Tiwari VK, Ezejiofor, AN, Okorie, A, Orisakwe, OE. 2013b. Hypoglycaemic
Mishra BB (eds), 1st edn. Research Signpost: Trivandrum; and tissue-protective effects of the aqueous extract of Persea
187–212. americana seeds on alloxan-induced albino rats.
Brai B, Odetola A, Agomo P. 2007a. Effects of Persea americana Fatema K, Zwar NA, Milton AH, Ali L, Rahman B. 2016. Prevalence
leaf extracts on body weight and liver lipids in rats fed of risk factors for cardiovascular diseases in bangladesh: a
hyperlipidaemic diet. Afr J Biotechnol 6: 1007–1011. systematic review and meta-analysis. PLoS One 11:
Brai BI, Odetola A, Agomo P. 2007b. Hypoglycemic and e0160180.
hypocholesterolemic potential of Persea americana leaf Fidrianny I, Soemardji AA, Umar MH. 2016. Lipid profile and
extracts. J Med Food 10: 356–360. platelet aggregation of ethanolic seed extract of avocado
Brai BI, Odetola AA, Akindele SK, Fesobi TW, Agomo PU. 2012. (Persea americana mill.) in hyperlipidemic male wistar rat.
Evaluation of antiperoxidative and antioxidant properties of Asian J Pharm Clin Res 9: 143–147.
aqueous and methanolic leaf extracts of Persea americana mill. Gallagher AM, Flatt PR, Duffy G, Abdel-Wahab YHA. 2003. The
In rats fed high lipid diet. Can J Pure Appl Sci 6: 2079–2088. effects of traditional antidiabetic plants on in vitro glucose
Carranza-Madrigal J, Herrera-Abarca JE, Alvizouri-Muñoz M, diffusion. Nutr Res 23: 413–424.
Alvarado-Jimenez MR, Chavez-Carbajal F. 1997. Effects of a Golan A, Kahn V, Sadovski AY. 1977. Relationship between
vegetarian diet vs. a vegetarian diet enriched with avocado in polyphenols and browning in avocado mesocarp. Comparison
hypercholesterolemic patients. Arch Med Res 28: 537–541. between the Fuerte and Lerman cultivars. J Agric Food Chem
Carranza J, Alvizouri M, Alvarado MR, Chávez F, Gómez M, 25: 1253–1260.
Herrera JE. 1995. Effects of avocado on the level of blood Gondwe M, Kamadyaapa D, Tufts M, Chuturgoon A, Ojewole J,
lipids in patients with phenotype II and IV dyslipidemias. Arch Musabayane C. 2007. Effects of Persea americana Mill
Inst Cardiol Mex 65: 342–348. (Lauraceae)[" Avocado"] ethanolic leaf extract on blood
Carvajal-Zarrabal O, Nolasco-Hipolito C, Aguilar-Uscanga MG, glucose and kidney function in streptozotocin-induced
Melo-Santiesteban G, Hayward-Jones PM, Barradas-Dermitz diabetic rats and on kidney cell lines of the proximal (LLCPK1)
DM. 2014a. Avocado oil supplementation modifies and distal tubules (MDBK). Methods Find Exp Clin Pharmacol
cardiovascular risk profile markers in a rat model of sucrose- 30: 25–35.
induced metabolic changes. Dis Markers 2014: 1–8. Gouegni EF, Abubakar H. 2013. Phytochemical, toxicological,
Carvajal-Zarrabal O, Nolasco-Hipolito C, Aguilar-Uscanga MG, biochemical and haematological studies on avocado
Melo Santiesteban G, Hayward-Jones PM, Barradas-Dermitz (Persea americana) in experimental animals. Niger Food J 31:
DM. 2014b. Effect of dietary intake of avocado oil and olive 64–69.
oil on biochemical markers of liver function in sucrose-fed rats. Grant WC. 1960. Influence of avocados on serum cholesterol. Exp
Biomed Res Int 2014: 1–8. Biol Med 104: 45–47.
CDC, 2012. Vital signs: awareness and treatment of uncontrolled Grundy SM, Cleeman JI, Daniels SR, et al. 2005. Diagnosis and
hypertension among adults--United States, 2003-2010, management of the metabolic syndrome. An American Heart
MMWR Morb Mortal Wkly Rep, 2012/09/07 ed., pp. 703–709. Association/National Heart, Lung, and Blood Institute
Christiansen BA, Bhatti S, Goudarzi R, Emami S. 2015. Scientific Statement 112: 2735–2752.
Management of osteoarthritis with avocado/soybean Hamouda AF. 2015. Study on the effect of avocado on apoptosis,
unsaponifiables. Cartilage 6: 30–44. oxidative stress and injuries induced by diethyl nitrosamine in
Collaboration, NCDRF. 2016. Worldwide trends in diabetes since rat liver. J Pharm Pharmacol 3: 243–252.
1980: a pooled analysis of 751 population-based studies with Hassani FV, Shirani K, Hosseinzadeh H. 2016. Rosemary
4·4 million participants. The Lancet 387: 1513–1530. (Rosmarinus officinalis) as a potential therapeutic plant in
Colquhoun DM, Moores D, Somerset SM, Humphries JA. 1992. metabolic syndrome: a review. Naunyn Schmiedebergs Arch
Comparison of the effects on lipoproteins and apolipoproteins Pharmacol 389: 931–949.
of a diet high in monounsaturated fatty acids, enriched Hosseini A, Hosseinzadeh H. 2015. A review on the effects of
with avocado, and a high-carbohydrate diet. Am J Clin Nutr Allium sativum (Garlic) in metabolic syndrome. J Endocrinol
56: 671–677. Invest 38: 1147–1157.
Del Toro-Equihua M, Velasco-Rodríguez R, López-Ascencio R, Hosseinzadeh H, Nassiri-Asl M. 2014. Review of the protective
Vásquez C. 2016. Effect of an avocado oil-enhanced diet effects of rutin on the metabolic function as an important
(Persea americana) on sucrose-induced insulin resistance in dietary flavonoid. J Endocrinol Invest 37: 783–788.
Wistar rats. J Food Drug Anal 24: 350–357. Imafidon K. 2010. Liver function status of hypertensive and
Dreher ML, Davenport AJ. 2013. Hass avocado composition normotensive rats administered Persea americana Mill.
and potential health effects. Crit Rev Food Sci Nutr 53: (Avocado) seeds. Acad J Plant Sci 3: 130–133.
738–750. Imafidon K, Amaechina F. 2010. Effects of aqueous seed extract of
Dzeufiet PDD, Mogueo A, Bilanda DC, et al. 2014. Persea americana Mill.(avocado) on blood pressure and lipid
Antihypertensive potential of the aqueous extract which profile in hypertensive rats. Adv Biol Res 4: 116–121.
combine leaf of Persea americana Mill. (Lauraceae), stems Izzo AA, Hoon-Kim S, Radhakrishnan R, Williamson EM. 2016. A
and leaf of Cymbopogon citratus (D.C) Stapf. (Poaceae), fruits critical approach to evaluating clinical efficacy, adverse events

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
836 J. TABESHPOUR ET AL.

and drug interactions of herbal remedies. Phytother Res 30: scavenger or 1-methylcyclopropene to extend storage life.
691–700. Food Chem 121: 1203–1210.
Jiménez-Arellanes A, Luna-Herrera J, Ruiz-Nicolás R, Cornejo- Mfonobong A, Ismail U, Mairo IH, Maimuna Z, Fatima D. 2013.
Garrido J, Tapia A, Yépez-Mulia L. 2013. Antiprotozoal and Hypolipidemic and antioxidant effects of petroleum ether and
antimycobacterial activities of Persea americana seeds. BMC methanolic fractions of Persea americana mill seeds in wistar
Complement Altern Med 13: 1–5. rats fed a high fat-high cholesterol diet. Int J Med Pharm Sci
Kahn V. 1983. Multiple effects of hydrogen peroxide on the 3: 1–10.
activity of avocado polyphenol oxidase. Phytochemistry 22: Miller M. 2009. Dyslipidemia and cardiovascular risk: the
2155–2159. importance of early prevention. QJM 102: 657–667.
Kawagishi H, Fukumoto Y, Hatakeyama M, et al. 2001. Liver injury Moghadasian MH, Frohlich JJ. 1999. Effects of dietary
suppressing compounds from avocado (Persea americana). J phytosterols on cholesterol metabolism and atherosclerosis:
Agric Food Chem 49: 2215–2221. clinical and experimental evidence. Am J Med 107: 588–594.
Koh H-H, Murray IJ, Nolan D, Carden D, Feather J, Beatty S. 2004. Mollazadeh H, Hosseinzadeh H. 2016. Cinnamon effects on
Plasma and macular responses to lutein supplement in metabolic syndrome: a review based on its mechanisms. Iran
subjects with and without age-related maculopathy: a pilot J Basic Med Sci 19: 1258–1270.
study. Exp Eye Res 79: 21–27. Monika P, Geetha A. 2015. The modulating effect of Persea
Kolawole O, Kolawole S, Ayankunle A, Olaniran I. 2012. Methanol americana fruit extract on the level of expression of fatty acid
leaf extract of Persea americana protects rats against synthase complex, lipoprotein lipase, fibroblast growth
cholesterol-induced hyperlipidemia. Br J Med Med Res 2: 235. factor-21 and leptin – A biochemical study in rats subjected
Kritchevsky D, Chen SC. 2005. Phytosterols—health benefits and to experimental hyperlipidemia and obesity. Phytomedicine
potential concerns: a review. Nutr Res 25: 413–428. 22: 939–945.
Kritchevsky D, Tepper SA, Wright S, Czarnecki SK, Wilson TA, Monika P, Geetha A. 2016. Effect of hydroalcoholic fruit extract of
Nicolosi RJ. 2003. Cholesterol vehicle in experimental Persea americana Mill. on high fat diet induced obesity: a dose
atherosclerosis 24: avocado oil. J Am Coll Nutr 22: 52–55. response study in rats. Indian J Exp Biol 54: 370–378.
Kumar B, Cumbal L. 2016. UV-Vis, FTIR and antioxidant study of Nagaraj M, Sandhya V, Supriya G, et al. 2010. Antioxidant and
Persea americana (Avocado) leaf and fruit: a comparison. antibacterial activity of avocado (Persea gratissima Gaertner)
Rev Fac Cienc Quim 14: 13–20. seed extract. World Appl Sci J 9: 695–698.
Lacerda LG, da Silva Carvalho Filho MA, Bauab T, et al. 2015. The Ahmed EM, Barmore CR. 1980. Avocado. In Tropical and
effects of heat-moisture treatment on avocado starch Subtropical Fruits: Composition, Properties and Uses, Nagy
granules. J Therm Anal Calorim 120: 387–393. S, Shaw PE (eds). AVI Pub. Co.: Westport, Connecticut;
Lerman-Garber I, Ichazo-Cerro S, Zamora-González J, Cardoso- 121–156.
Saldaña G, Posadas-Romero C. 1994. Effect of a high- Naveh E, Werman MJ, Sabo E, Neeman I. 2002. Defatted avocado
monounsaturated fat diet enriched with avocado in NIDDM pulp reduces body weight and total hepatic fat but increases
patients. Diabetes Care 17: 311. plasma cholesterol in male rats fed diets with cholesterol. J
Li Z, Wong A, Henning SM, et al. 2013. Hass avocado modulates Nutr 132: 2015–2018.
postprandial vascular reactivity and postprandial inflammatory Nwaoguikpe R, Braide W. 2011. The effect of aqueous seed extract
responses to a hamburger meal in healthy volunteers. Food of Persea americana (avocado pear) on serum lipid and
Funct 4: 384–391. cholesterol levels in rabbits. Afr J Pharm Pharmacol 1: 23–29.
Lima CR, Vasconcelos CFB, Costa-Silva JH, et al. 2012. Anti-diabetic Oboh G. 2014. Inhibitory effect of phenolic extract from leaf and fruit
activity of extract from Persea americana Mill. leaf via the of avocado pear (Persea americana) on fe2+ induced lipid
activation of protein kinase B (PKB/Akt) in streptozotocin- peroxidation in rats’pancreas in vitro. Futa J Res Sci 9: 276–286.
induced diabetic rats. J Ethnopharmacol 141: 517–525. Oboh G, Ademosun AO, Akinleye M, Omojokun OS, Boligon AA,
Liu X, Robinson PW, Madore MA, Witney GW, Arpaia ML. 1999. Athayde ML. 2015. Starch composition, glycemic indices,
`Hass’ avocado carbohydrate fluctuations. II. Fruit growth phenolic constituents, and antioxidative and antidiabetic
and ripening. J Am Soc Hort Sci 124: 676–681. properties of some common tropical fruits. J Ethn Foods 2:
López Ledesma R, Frati Munari AC, Hernández Domínguez BC, 64–73.
et al. 1996. Monounsaturated fatty acid (avocado) rich diet Oboh G, Odubanjo VO, Bello F, et al. 2016. Aqueous extracts of
for mild hypercholesterolemia. Arch Med Res 27: 519–523. avocado pear (Persea americana Mill.) leaves and seeds exhibit
Lu Q-Y, Arteaga JR, Zhang Q, Huerta S, Go VLW, Heber D. 2005. anti-cholinesterases and antioxidant activities in vitro. J Basic
Inhibition of prostate cancer cell growth by an avocado Clin Physiol Pharmacol 27: 131–140.
extract: role of lipid-soluble bioactive substances. J Nutr Odubanjo V, Oboh G, Makinde O. 2016. Inhibitory effect of aqueuos
Biochem 16: 23–30. extracts of avocado pear (Persea americana) leaf and seed on
Lu Q-Y, Zhang Y, Wang Y, et al. 2009. California hass avocado: angiotensin 1-converting enzyme: a possible means in
profiling of carotenoids, tocopherol, fatty acid, and fat content treating/managing hypertension. J Appl Life Sci Int 4: 1–9.
during maturation and from different growing areas. J Agric Ojewole JA, Amabeoku GJ. 2006. Anticonvulsant effect of Persea
Food Chem 57: 10408–10413. americana Mill (Lauraceae) (Avocado) leaf aqueous extract in
Mackay J, Mensah GA, Mendis S, Greenlund K. 2004. The Atlas of mice. Phytother Res 20: 696–700.
Heart Disease and Stroke. World Health Organization: Geneva. Ojewole JA, Kamadyaapa DR, Gondwe MM, Moodley K,
Mahadeva Rao U, Adinew B. 2011. Hypolipidemic effect of Musabayane CT. 2007. Cardiovascular effects of Persea
dichloromethane as well as methanolic fruit and leaf extract americana Mill (Lauraceae) (avocado) aqueous leaf extract in
of ethiopian alligator pear (Persea americana mill.) on experimental animals. Cardiovasc J Afr 18: 69–76.
tyloxapol-induced hyperlipidemic experimental rat. Asian J Olaniyan MF. 2014. Effect of liquid extract of pear avocado leaf
Res Chem 4: 574–574. (Persea americana) on plasma levels of aminotransferases,
Mahadeva Rao U, Ponnusamy K, Naidu JR, Sundaram CS. 2014. cholesterol and total bile acids in hypertensive patients. Am
Modulatory influence of avocado on renal oxido-lipidemic J Med Sci 4: 87–91.
stress and mRNA expression of NOS in renal artery studied Ortiz-Avila O, Esquivel-Martinez M, Olmos-Orizaba BE, Saavedra-
in nephropathy induced rats. Int Med J 21: 1–7. Molina A, Rodriguez-Orozco AR, Cortes-Rojo C. 2015a. Avocado
Mahmoed MY, Rezq AA. 2013. Hepatoprotective effect of oil improves mitochondrial function and decreases oxidative
avocado fruits against carbon tetrachloride-induced liver stress in brain of diabetic rats. J Diabetes Res 2015: 1–9.
damage in male rats. World Appl Sci J 21: 1445–1452. Ortiz-Avila O, Gallegos-Corona MA, Sánchez-Briones LA, et al.
Malik S, Wong ND, Franklin SS, et al. 2004. Impact of the 2015b. Protective effects of dietary avocado oil on impaired
metabolic syndrome on mortality from coronary heart disease, electron transport chain function and exacerbated oxidative
cardiovascular disease, and all causes in united states adults. stress in liver mitochondria from diabetic rats. J Bioenerg
Circulation 110: 1245–1250. Biomembr 47: 337–353.
Marrero-Faz E, Sanchez-Calero J, Young L, Harvey A. 2014. Ortiz Moreno, A, Hernandez Navarro, M, Dorantes Alvrez, L,
Inhibitory effect of Persea americana mill leaf aqueous extract Chamorro Cevallos, G, Hernandez Ortega, M, 2007.
and its fractions on PTP1B as therapeutic target for type 2 Comparative study of the hypolipidemic effect induced by
diabetes. B LATINOAM CARIBE PL 13: 144–151. different monounsaturated avocado oils, Proceedings VI
Meyer MD, Terry LA. 2010. Fatty acid and sugar composition of World Avocado Congress (Acts VI Congreso Mundial del
avocado, cv. Hass, in response to treatment with an ethylene Aguacate). Vina Del Mar, Chile. pp. 12–16.

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)
AVOCADO AND METABOLIC SYNDROME 837

Owolabi M, Coker H, Jaja S. 2010. Bioactivity of the from avocado (Persea americana) pulp with antiplatelet and
phytoconstituents of the leaves of Persea americana. J Med antithrombotic activities. Food Funct 6: 192–202.
Plants Res 4: 1130–1135. Rouhi-Boroujeni H, Rouhi-Boroujeni H, Gharipour M,
Owolabi MA, Jaja SI, Coker HAB. 2005. Vasorelaxant action of Mohammadizadeh F, Ahmadi S, Rafieian-kopaei M. 2015.
aqueous extract of the leaves of Persea americana on isolated Systematic review on safety and drug interaction of herbal
thoracic rat aorta. Fitoterapia 76: 567–573. therapy in hyperlipidemia: a guide for internist. Acta Biomed
Oyeyemi A, Oyeyemi R. 2015. Effect of the aqueous extract of the 86: 130–136.
leaves and seeds of avocado pear (Persea Americana) on some Sabaté J, Wien M, Haddad E. 2015. Post-ingestive effects of
marker enzymes and cholesterol in the albino rat tissues. IOSR avocados in meals on satiety and gastric hormone blood
J Environ Sci Toxicol Food Technol 9: 15–18. levels. Human Health Nut 459–461.
Ozdemir F, Topuz A. 2004. Changes in dry matter, oil content and Salazar MJ, El Hafidi M, Pastelin G, Ramírez-Ortega MC,
fatty acids composition of avocado during harvesting time and Sánchez-Mendoza MA. 2005. Effect of an avocado oil-rich
post-harvesting ripening period. Food Chem 86: 79–83. diet over an angiotensin II-induced blood pressure response.
Ozolua R, Anaka O, Okpo S, Idogun S. 2009. Acute and sub-acute J Ethnopharmacol 98: 335–338.
toxicological assessment of the aqueous seed extract of Shehata M, Soltan SS. 2013. Effects of bioactive component
Persea americana Mill (Lauraceae) in rats. Afr J Tradit of kiwi fruit and avocado (fruit and seed) on
Complement Altern Med 6: 573–578. hypercholesterolemic rats. World J Dairy Food Sci 8: 82–93.
Padmanabhan M, Arumugam G. 2014. Effect of Persea americana Smith CJ, Ryckman KK. 2015. Epigenetic and developmental
(avocado) fruit extract on the level of expression of influences on the risk of obesity, diabetes, and metabolic
adiponectin and PPAR-γ in rats subjected to experimental syndrome. Diabetes Metab Syndr Obes 8: 295–302.
hyperlipidemia and obesity. J Complement Integr Med 11: Sudhir K. 2005. Lipoprotein-associated phospholipase A2, a
107–119. novel inflammatory biomarker and independent risk predictor
Pahua-Ramos ME, Garduño-Siciliano L, Dorantes-Alvarez L, et al. for cardiovascular disease. J Clin Endocrinol Metab 90:
2014. Reduced-calorie avocado paste attenuates metabolic 3100–3105.
factors associated with a hypercholesterolemic-high fructose Thenmozhi A, Shanmugasundaram C, Rao UM. 2012.
diet in rats. Plant Foods Hum Nutr 69: 18–24. Biochemical evaluation of anti-diabetic phytomolecule
Pahua-Ramos ME, Ortiz-Moreno A, Chamorro-Cevallos G, et al. through bioactivity guided solvent fractionation and
2012. Hypolipidemic effect of avocado (Persea americana subfractionation from hydromethanolic (2: 3) extract of
Mill) seed in a hypercholesterolemic mouse model. Plant Foods Alligator pear Fruit in streptozotocin induced diabetic rats.
Hum Nutr 67: 10–16. J Appl Pharm Sci 2: 61.
Papathanasiou G, Zerva E, Zacharis I, et al. 2015. Association of Unlu NZ, Bohn T, Clinton SK, Schwartz SJ. 2005. Carotenoid
high blood pressure with body mass index, smoking and absorption from salad and salsa by humans is enhanced
physical activity in healthy young adults. Open Cardiovasc by the addition of avocado or avocado oil. J Nutr 135:
Med J 9: 5–17. 431–436.
Paul R, Kulkarni P, Ganesh N. 2011. Avocado fruit (Persea Uysal S, Zengin G, Aktumsek A, Karatas S. 2015. Fatty acid
americana Mill) exhibits chemo-protective potentiality against composition, total sugar content and anti-diabetic activity of
cyclophosphamide induced genotoxicity in human lymphocyte methanol and water extracts of nine different fruit tree leaves
culture. J Exp Ther Oncol 9: 221–230. collected from mediterranean region of turkey. Int J Food Prop
Pieterse Z. 2003. Avocados (monounsaturated fatty acids), 18: 2268–2276.
weight loss and serum lipids. Energy (kJ) 3: 65–71. Vekiari SA, Papadopoulou PP, Lionakis S, Krystallis A. 2004.
Pieterse Z, Jerling JC, Oosthuizen W, et al. 2005. Substitution of Variation in the composition of Cretan avocado cultivars
high monounsaturated fatty acid avocado for mixed dietary during ripening. J Sci Food Agric 84: 485–492.
fats during an energy-restricted diet: effects on weight loss, Wang L, Bordi PL, Fleming JA, Hill AM, Kris-Etherton PM. 2015.
serum lipids, fibrinogen, and vascular function. Nutrition 21: Effect of a moderate fat diet with and without avocados on
67–75. lipoprotein particle number, size and subclasses in overweight
Piironen V, Lindsay DG, Miettinen TA, Toivo J, Lampi AM. 2000. and obese adults: a randomized, controlled trial. J Am Heart
Plant sterols: biosynthesis, biological function and their Assoc 4: e001355.
importance to human nutrition. J Sci Food Agric 80: Wang M, Zheng Y, Khuong T, Lovatt CJ. 2016. Developmental
939–966. differences in antioxidant compounds and systems in normal
Pradeep G, Naresh A, Reddy GN, Reddy VR, Kotaiah S. 2012. and small-phenotype fruit of ‘Hass’ avocado (Persea americana
Anti-microbial and anti-diabetic activity of Prosopis chilensis Mill.). Sci Hortic (Amsterdam) 206: 15–23.
extract against alloxan-induced diabetic rats. Int J Res Pharm Wang W, Bostic TR, Gu L. 2010. Antioxidant capacities,
Nanosci 1: 139–146. procyanidins and pigments in avocados of different strains
Rao USM, Adinew B. 2011. Remnant b-cell-stimulative and anti- and cultivars. Food Chem 122: 1193–1198.
oxidative effects of Persea americana fruit extract studied in Werman MJ, Neeman I, Mokady S. 1991. Avocado oils and
rats introduced into streptozotocin - induced hyperglycaemic hepatic lipid metabolism in growing rats. Food Chem Toxicol
state. Afr J Tradit Complement Altern Med 8: 210–217. 29: 93–99.
Razavi BM, Hosseinzadeh H. 2014. A review of the effects of Wien M, Haddad E, Oda K, Sabaté J. 2013. A randomized 3x3
Nigella sativa L. and its constituent, thymoquinone, in crossover study to evaluate the effect of Hass avocado intake
metabolic syndrome. J Endocrinol Invest 37: 1031–1040. on post-ingestive satiety, glucose and insulin levels, and
Razavi BM, Hosseinzadeh H. 2016. Saffron: a promising natural subsequent energy intake in overweight adults. Nutr J 12: 1.
medicine in the treatment of metabolic syndrome. J Sci Food Wientarsih I, Madyastuti R, Prasetyo BF, Aldobrata A. 2012. Anti-
Agric https://doi.org/10.1002/jsfa.8134. [Epub ahead of lithiasis activity of avocado (Persea americana Mill) Leaves
print] Extract in White Male Rats. HAYATI J Biosci 19: 49–52.
Rodríguez-Carpena JG, Morcuende D, Estévez M. 2011. Avocado Wu SH, Liu Z, Ho SC. 2010. Metabolic syndrome and all-cause
by-products as inhibitors of color deterioration and lipid and mortality: a meta-analysis of prospective cohort studies. Eur
protein oxidation in raw porcine patties subjected to chilled J Epidemiol 25: 375–384.
storage. Meat Sci 89: 166–173. Xiong XJ, Wang PQ, Li SJ, Li XK, Zhang YQ, Wang J. 2015. Garlic
Rodriguez-Sanchez DG, Flores-Garcia M, Silva-Platas C, et al. for hypertension: a systematic review and meta-analysis of
2015. Isolation and chemical identification of lipid derivatives randomized controlled trials. Phytomedicine 22: 352–361.

Copyright © 2017 John Wiley & Sons, Ltd. Phytother. Res. 31: 819–837 (2017)

You might also like